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Answers to G-1 through G-50 (Pathology, GMC Nirmal)

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G-1 (Page 1)

1. Cellular adaptation: Squamous metaplasia - transformation of the normal columnar epithelium of the endocervix into stratified squamous epithelium.
2. Causative agent: Human Papillomavirus (HPV), particularly low-risk types (HPV 6, 11); also chronic irritation/inflammation (e.g., Trichomonas vaginalis, repeated trauma).
3. Long-term complication: Dysplasia progressing to Cervical Intraepithelial Neoplasia (CIN) and eventually Squamous Cell Carcinoma of the cervix (especially if caused by high-risk HPV types 16, 18).

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G-2 (Page 2)

1. Diagnosis: Acute Tubular Necrosis (ATN) - ischemic type. Grossly: pale, swollen kidney. Microscopically: necrosis of tubular epithelial cells, especially the proximal convoluted tubules and thick ascending limb of loop of Henle, with intact tubular basement membrane.
2. Forms of Reversible Cell Injury:
   • Cellular swelling (hydropic change)
   • Fatty change (steatosis)
   • Hyaline change
   • Mucoid change
   • Glycogen infiltration

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G-3 (Page 3)

1. Diagnosis: Fatty liver (Hepatic steatosis) / Alcoholic steatosis. Grossly: enlarged, yellow, greasy liver. Microscopically: macrovesicular fat globules (large fat vacuoles displacing the nucleus to the periphery) in hepatocytes.
2. Special stain: Oil Red O (on frozen sections) stains fat orange-red. Alternatively, Sudan III or Sudan Black B. (H&E shows clear vacuoles; confirmation requires Oil Red O on frozen tissue.)

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G-4 (Page 4)

1. (Question 1 not shown fully - Diagnosis: Amyloidosis)
2. Physical properties and classification of amyloid:
   • Physical properties: Amorphous, homogeneous, hyaline, eosinophilic; non-branching fibrils 7.5-10 nm diameter; beta-pleated sheet configuration; apple-green birefringence under polarised light with Congo Red stain; metachromatic with crystal violet.
   • Classification:
     • AL (Amyloid Light chain) - from immunoglobulin light chains (plasma cell dyscrasias/myeloma)
     • AA (Amyloid-Associated) - from serum amyloid A protein (chronic inflammatory conditions)
     • Aβ - Alzheimer's disease
     • Aβ2M - haemodialysis-associated
     • ATTR - transthyretin (familial and senile)
3. Bone marrow biopsy: Would show increased plasma cells (>10%) - consistent with Multiple Myeloma. Plasma cells may show "clock-face" or "cartwheel" chromatin pattern (Mott cells, Russell bodies). Diagnosis of myeloma requires >10% clonal plasma cells.

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G-5 (Page 5)

1. Diagnosis: Tuberculous lymphadenitis (Scrofula). Grossly: matted lymph nodes with central caseation (cheese-like material). Microscopically: Caseating granulomas - central area of caseous necrosis surrounded by epithelioid cells, Langhans giant cells, lymphocytes, and a peripheral rim of fibrosis.
2. Causative organism: Mycobacterium tuberculosis. Special stain: Ziehl-Neelsen (ZN) stain - identifies acid-fast bacilli (AFB) that appear as red rods against a blue background.

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G-6 (Page 6)

1. Type of necrosis: Fibrinoid necrosis - a specific form of necrosis seen in immune complex-mediated vasculitis, characterised by deposition of fibrin-like material in vessel walls giving a bright pink (eosinophilic) smudgy appearance.
2. Substance deposited in vessel wall: Immune complexes (antigen-antibody complexes, specifically DNA-anti-DNA complexes in SLE) along with fibrin, complement components (C3, C1q), and immunoglobulins (IgG, IgM).

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G-7 (Page 7)

1. Lesion: Dry gangrene of the foot/toes (due to peripheral vascular disease in diabetes - diabetic angiopathy).
2. Type of necrosis: Coagulative necrosis. In dry gangrene, the tissues are desiccated, mummified, and the tissue architecture is preserved (coagulative pattern). The boundary between viable and dead tissue is distinct.

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G-8 (Page 8)

1. Type of necrosis: Fat necrosis (enzymatic/saponification fat necrosis). Grossly: chalky-white, opaque deposits on omentum (calcium soap deposits). Microscopically: ghost outlines of fat cells with granular basophilic calcium deposits (saponification), surrounded by inflammatory cells.
2. Abdominal emergency: Acute pancreatitis - released pancreatic lipases cause enzymatic digestion of peripancreatic and omental fat.

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G-9 (Page 9)

1. Structures shown: Calcified plaques in the tunica media of arteries (showing calcification of the media with uninvolved intima).
2. Type of calcification: Monckeberg's medial calcific sclerosis (dystrophic calcification) - calcium deposits in the media of medium-sized muscular arteries in the absence of atherosclerosis or intimal thickening. The intima is uninvolved. It does not narrow the lumen by itself. Seen in diabetics and the elderly.

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G-10 (Page 10)

1. Pathway: Apoptosis (programmed cell death).
2. Enzymes activated: Caspases (specifically initiator caspases - caspase-8 in extrinsic pathway, caspase-9 in intrinsic/mitochondrial pathway; and executioner caspases - caspase-3, caspase-6, caspase-7).
3. Change in cell membrane: Phosphatidylserine (PS) flip - phosphatidylserine normally located on the inner leaflet of the plasma membrane is translocated to the outer leaflet (externalised), serving as an "eat-me" signal for phagocytes (macrophages recognise it via annexin V).

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G-11 (Page 11)

• Embryogenesis: organ morphogenesis (digit separation, neural tube formation)
• Thymic deletion of autoreactive T-cells (immune tolerance)
• Hormone-dependent involution (endometrium, prostate)
• Elimination of cells after immune response (lymphocyte deletion)
• Cell deletion in proliferating cell populations (intestinal crypts)
• Elimination of potentially harmful cells (tumour cells, virally infected cells)
• No inflammation (unlike necrosis) because contents are packaged in apoptotic bodies and phagocytosed

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G-12 (Page 12)

1. History and examination - duration, fever, weight loss, hepatosplenomegaly
2. Blood investigations:
   • CBC with differential - lymphocytosis, atypical lymphocytes
   • ESR, CRP
   • LFT, RFT
   • Mantoux/Tuberculin skin test
   • Monospot test (EBV)
   • Serology: EBV, CMV, HIV, Toxoplasma
3. Imaging: Chest X-ray (hilar adenopathy - TB, sarcoidosis, lymphoma), CT neck/chest/abdomen
4. FNAC (Fine Needle Aspiration Cytology) of the most accessible node
5. Lymph node biopsy (excision biopsy) - most definitive; for histopathology, culture (TB), flow cytometry (lymphoma)
6. Special stains on biopsy: ZN stain for AFB, PAS, GMS (if fungal), immunohistochemistry for lymphoma markers

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G-13 (Page 13)

1. Organ identification and changes (a vs b): This typically shows uterus - enlarged uterus (a) vs normal (b), suggesting hypertrophy/hyperplasia. The diseased organ is larger with thickened walls (hypertrophy) or increased number of cells (hyperplasia).
2. Most likely cellular adaptation: Hypertrophy (increase in cell size) and/or Hyperplasia (increase in cell number).
3. Physiological conditions: Pregnancy (uterine hypertrophy + hyperplasia), skeletal muscle hypertrophy with exercise, cardiac hypertrophy in athletes. Pathological conditions: Left ventricular hypertrophy in hypertension, prostatic hyperplasia (BPH), endometrial hyperplasia, adrenal hyperplasia.

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G-14 (Page 14)

1. Cellular adaptation: Atrophy - reduction in cell size (and number in some cases), leading to a decrease in organ/tissue size.
2. Physiological conditions: Ageing (senile atrophy - brain, gonads), uterine involution post-partum, thymic involution. Pathological conditions: Disuse atrophy (limb immobilisation), denervation atrophy (polio), ischaemic atrophy, pressure atrophy, endocrine atrophy (adrenal atrophy after steroid withdrawal).
3. Mechanisms of atrophy:
   • Decreased protein synthesis
   • Increased protein degradation via ubiquitin-proteasome pathway
   • Autophagy (lysosomal degradation of cellular components)
   • Apoptosis
   • Reduced growth factor signalling (e.g., IGF-1, PI3K/Akt pathway downregulation)

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G-15 (Page 15)

1. Type of necrosis: Coagulative necrosis
2. Common causes:
   • Ischaemia/infarction (most common) - especially in kidney, heart, spleen
   • Bacterial toxins
   • Chemical injury
3. Different morphological patterns of necrosis:
   • Coagulative necrosis (ischaemia - most organs)
   • Liquefactive necrosis (brain infarct, bacterial abscess)
   • Caseous necrosis (tuberculosis)
   • Fat necrosis (pancreatitis, trauma)
   • Fibrinoid necrosis (immune complex vasculitis, SLE)
   • Gangrenous necrosis (dry/wet/gas gangrene)

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G-16 (Page 16)

1. Type of necrosis: Liquefactive necrosis
2. Common causes:
   • Bacterial infections (pyogenic/suppurative - abscess formation)
   • Brain infarction (CNS undergoes liquefactive necrosis due to high lipid content and abundant hydrolytic enzymes)
   • Fungal infections
3. Different morphological patterns of necrosis: (same as above)
   • Coagulative, Liquefactive, Caseous, Fat, Fibrinoid, Gangrenous necrosis

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G-17 (Page 17)

1. Type/pattern of necrosis: Coagulative necrosis
2. Common cause: Ischaemia/infarction (occlusion of blood supply)
3. Architecture preserved? Yes, the tissue architecture (cell outlines, ghostly outlines of cells) is preserved in coagulative necrosis. Reason: Denaturation of structural proteins and enzymes occurs simultaneously, which inhibits proteolysis, thereby maintaining the basic cellular framework (ghost cells).
4. Gross appearance of localised area: Infarct (pale/white infarct in solid organs like kidney, heart; red/haemorrhagic infarct in loose-textured organs or organs with dual blood supply).

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G-18 (Page 18)

1. Pigment: Homogentisic acid (Alkapton). Also called Alkapton.
2. Disease: Alkaptonuria (also called Ochronosis when the pigment is deposited in tissues) - an autosomal recessive disorder due to deficiency of homogentisic acid oxidase (homogentisate 1,2-dioxygenase), leading to accumulation of homogentisic acid.
3. Other black endogenous pigment: Melanin (produced by melanocytes from tyrosine via DOPA). Also: carbon/coal dust (exogenous but deposits in tissue).

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G-19 (Page 19)

1. Reason for colour change (Image A): Breakdown of haemoglobin from extravasated red blood cells. Sequential changes:
   • Initially red (oxyhaemoglobin)
   • Then blue-purple (deoxyhaemoglobin)
   • Then green (biliverdin)
   • Then yellow (bilirubin)
   • Finally yellow-brown/fading (haemosiderin + resorption)
2. Pigment in Image B: Haemosiderin - a golden-brown, granular pigment formed by aggregation of ferritin micelles. It is the iron-storage form resulting from haemoglobin breakdown.
3. Special stain in Image C: Perl's Prussian Blue stain (Perls' stain) - stains haemosiderin (ferric iron) bright blue.

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G-20 (Page 20)

1. Brown-gold pigment: Lipofuscin ("wear and tear pigment") - a golden-brown, finely granular intracytoplasmic pigment representing indigestible residues of lipid peroxidation (oxidised lipids and proteins). Seen in perinuclear location in cardiomyocytes and hepatocytes of elderly individuals.
2. Other pigments:
   • Haemosiderin (iron-containing, golden-brown)
   • Melanin (brown-black)
   • Bilirubin (yellow)
   • Homogentisic acid/Alkapton (brown-black in ochronosis)
   • Carbon/coal dust (black - exogenous)
   • Anthracosis (carbon in lung - black)
3. Wear and tear pigment: Lipofuscin. It accumulates in post-mitotic cells (neurons, cardiac muscle) with ageing as a result of lipid peroxidation. It is not harmful per se but indicates cellular ageing. Also called ceroid when seen in pathological states. Associated with "brown atrophy" of heart and liver.

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G-21 (Page 21)

1. Organ: (Likely appendix or liver with congestion/inflammation). The lesions include: congestion, oedema, neutrophil infiltration.
2. Microscopic features: Vascular congestion, oedema of interstitium, neutrophil infiltration, possibly fibrin exudate.
3. Process of leucocyte migration: Extravasation/Diapedesis - leucocytes move from vessel lumen to tissue (interstitium) via:
   • Margination and Rolling (selectin-mediated)
   • Adhesion (integrin-ICAM mediated)
   • Transmigration/Diapedesis (through endothelial junctions)
   • Chemotaxis (directed migration toward chemoattractants)
4. Substances facilitating migration (chemotactic factors):
   • IL-8 (CXCL8) - major neutrophil chemoattractant
   • C5a (complement fragment)
   • Leukotriene B4 (LTB4)
   • Bacterial products (fMLP - N-formyl-methionyl peptides)

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G-22 (Page 22)

1. Lesion: Acute suppurative inflammation / early abscess formation. Microscopically: dense neutrophil infiltration, oedema, vascular congestion.
2. Opsonins aiding microbe binding for phagocytosis:
   • IgG (Fc portion binds Fc receptors on phagocytes)
   • C3b (complement fragment binds complement receptors CR1 on phagocytes)
   • Collectins (mannose-binding lectin)
   • Fibronectin
3. Phagocytic process steps:
   • Recognition and attachment (opsonin-receptor binding)
   • Engulfment (pseudopod extension, phagosome formation)
   • Killing and degradation - via oxygen-dependent (MPO-H2O2-halide system, reactive oxygen species) and oxygen-independent mechanisms (defensins, lysozyme, lactoferrin, elastase, cathepsin G)

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G-23 (Page 23)

1. Disorder in spleen: Amyloidosis of the spleen. Two patterns:
   • "Sago spleen" - amyloid deposits in the white pulp (follicles) giving a sago grain appearance
   • "Lardaceous spleen" - amyloid deposits in the red pulp (sinusoids) giving a waxy/lard-like appearance; spleen is enlarged.
2. Special stain: Congo Red stain - amyloid stains pink/salmon-red with Congo Red.
3. Under polarising microscope: Apple-green birefringence (dichroism) - the Congo Red-stained amyloid shows characteristic apple-green birefringence under cross-polarised light. This is pathognomonic of amyloid.

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G-24 (Page 24)

1. Organ: Appendix
2. Gross appearance: Enlarged, congested, dull serosal surface with fibrinopurulent exudate; lumen may contain pus (empyema). Microscopic appearance: Transmural neutrophilic infiltration of all layers (mucosa, submucosa, muscularis, serosa), mucosal ulceration, vascular congestion, oedema, fibrin deposition on serosa.
3. Likely diagnosis: Acute appendicitis (acute suppurative/phlegmonous appendicitis)
4. Morphological patterns of acute inflammation:
   • Serous inflammation (watery exudate - skin blisters)
   • Fibrinous inflammation (fibrin-rich exudate - pericarditis, pleuritis)
   • Suppurative/Purulent inflammation (pus formation - abscess, empyema)
   • Ulcerative inflammation (mucosal surface necrosis with ulcer formation - peptic ulcer)
   • Pseudomembranous inflammation (membrane of fibrin + cells on mucosal surface - C. difficile colitis, diphtheria)
   • Haemorrhagic inflammation

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G-25 (Page 25)

1. Diagnosis: Crohn's disease (granulomatous ileocolitis)
2. Granulomatous inflammation: A form of chronic inflammation characterised by collections of activated macrophages (epithelioid cells) surrounded by lymphocytes, with or without multinucleated giant cells (Langhans or foreign body type). It is a T-cell mediated (Type IV hypersensitivity) response to persistent, poorly degradable antigens.
3. Diseases with granulomatous inflammation:
   • Tuberculosis (caseating granulomas)
   • Sarcoidosis (non-caseating)
   • Crohn's disease (non-caseating)
   • Leprosy
   • Syphilis
   • Fungal infections (histoplasmosis, blastomycosis)
   • Foreign body reaction
   • Berylliosis
4. Types of granulomas:
   • Immune (hypersensitivity) granulomas - T-cell mediated (TB, sarcoid, Crohn's, leprosy)
   • Foreign body granulomas - formed around indigestible material (sutures, talc, silica), foreign body giant cells present
5. Gross appearance (Crohn's): "Cobblestone" mucosal appearance, "skip lesions" (segmental involvement), "hose-pipe" narrowing due to transmural fibrosis, creeping fat (fat wrapping), thickened rubbery bowel wall.

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G-26 (Page 26)

1. Steps in leucocyte extravasation:
   • Margination - leucocytes move to periphery of vessel lumen
   • Rolling - selectin-mediated loose adhesion (P-selectin, E-selectin on endothelium; PSGL-1 on leucocytes)
   • Adhesion/Sticking - integrin-mediated firm adhesion (ICAM-1/VCAM-1 on endothelium; LFA-1, Mac-1 on leucocytes)
   • Transmigration/Diapedesis - leucocytes crawl between endothelial cells (PECAM-1/CD31 mediated)
   • Chemotaxis - directed migration along chemical gradient toward site of injury
2. Changes in blood vessels during acute inflammation:
   • Transient vasoconstriction (seconds) followed by vasodilation (arterioles and venules)
   • Increased vascular permeability (endothelial contraction, gaps formation)
   • Slowing of blood flow / stasis
   • Increased hydrostatic pressure leading to exudate formation

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G-27 (Page 27)

1. Dominant cells: Lymphocytes (B cells in follicles/germinal centres; T cells in paracortex). In granulomatous lesions: epithelioid macrophages and Langhans giant cells.
2. Two pathways by which these cells are activated:
   • Antigen-dependent activation via antigen presenting cells (APCs/dendritic cells) presenting antigens via MHC molecules to T-cell receptors (TCR) - requires co-stimulatory signals (CD28-B7 interaction)
   • Cytokine-mediated activation - IL-2 (T-cell proliferation), IL-12 (Th1 differentiation), IL-4 (Th2 differentiation), IFN-γ (macrophage activation)

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G-28 (Page 28)

1. Diagnosis: Pulmonary Tuberculosis (Primary progressive or Post-primary/Secondary TB with cavitation)
2. Other causes of haemoptysis:
   • Bronchiectasis
   • Lung carcinoma
   • Pulmonary embolism/infarction
   • Bronchitis / pneumonia
   • Mitral stenosis
   • Goodpasture syndrome
   • Wegener's granulomatosis (GPA)
   • Aspergilloma
3. Microscopic features (TB): Caseating granulomas - central caseous necrosis (acellular, eosinophilic, cheese-like), surrounded by epithelioid macrophages, Langhans giant cells (horseshoe-shaped peripheral nuclei), lymphocytes, plasma cells, and peripheral fibrosis.
4. Pleural fluid analysis in TB pleuritis:
   • Exudate (high protein >3 g/dL, LDH elevated)
   • Lymphocyte predominant (>80% lymphocytes)
   • Low glucose
   • Elevated ADA (Adenosine Deaminase) >40 IU/L - highly suggestive
   • Protein/LDH ratio consistent with exudate (Light's criteria)
   • AFB smear usually negative; culture positive in ~30%

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G-29 (Page 29)

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G-30 (Page 30)

1. Lesion: Keloid
2. Substance deposited in excess: Type I and Type III collagen (predominantly Type I) - thick, haphazardly arranged ("whorled" or "glassy") collagen bundles are the hallmark. Keloids contain more collagen, proteoglycans, and myofibroblasts than hypertrophic scars.

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G-31 (Page 31)

1. Diagnosis: Hypertrophic scar (or Keloid if exceeds wound boundaries - context suggests keloid given post-suture mass)
2. Etiology:
   • Excessive fibroblast proliferation and collagen synthesis
   • Altered balance between collagen synthesis and degradation (reduced collagenase activity)
   • Genetic predisposition (more common in dark-skinned individuals)
   • Abnormal wound tension
3. Types of wound healing:
   • Primary intention (healing by first intention): Clean incised wound with approximated edges; minimal granulation tissue; heals with thin scar (e.g., surgical incision).
   • Secondary intention (healing by second intention): Open wound with widely separated edges; extensive granulation tissue formation; wound contraction by myofibroblasts; heals with larger scar (e.g., large skin ulcer, abscess cavity).
   • Tertiary intention (delayed primary closure): Wound left open initially (due to infection), then closed surgically after a few days.

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G-32 (Page 32)

1. Gross and histologic change - name: Granulation tissue (named because it has a pink, granular, glistening gross appearance due to many capillary loops with surrounding fibroblasts). Histologically: proliferating capillary loops (angiogenesis), myofibroblasts/fibroblasts, loose extracellular matrix (type III collagen early), inflammatory cells (especially macrophages).
2. Dermal cells that transitioned from G0 to G1: Fibroblasts (normally in G0 quiescent state) are stimulated to re-enter the cell cycle (G1 phase) and proliferate.
3. Growth factors responsible for this transition:
   • PDGF (Platelet-Derived Growth Factor) - from platelets, macrophages; stimulates fibroblast proliferation
   • FGF (Fibroblast Growth Factor) - especially bFGF/FGF-2; promotes angiogenesis and fibroblast growth
   • TGF-β (Transforming Growth Factor-beta) - stimulates collagen synthesis and fibroblast migration
   • EGF (Epidermal Growth Factor) and TGF-α - epithelial and fibroblast proliferation
   • VEGF (Vascular Endothelial Growth Factor) - angiogenesis in granulation tissue

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G-33 (Page 33)

1. Microscopic findings: Iliac vein: organized thrombus with fibrin, RBCs, neutrophils, and early recanalisation channels. Lung: haemorrhagic infarct - wedge-shaped area with coagulative necrosis, preserved architecture, haemorrhage.
2. Differentiation of antemortem vs postmortem clots:
   • Antemortem: Firm, dry, adherent, Lines of Zahn present, dull red/grey
   • Postmortem: Soft, gelatinous, non-adherent, no Lines of Zahn, "chicken fat" + red currant jelly appearance
3. Gross description of lung: Wedge-shaped, haemorrhagic (red) infarct at the periphery, with the apex pointing toward the hilum. The pleural surface may show fibrinous exudate.
4. Relationship of iliac vein to pulmonary lesion: Deep vein thrombosis (DVT) in the right iliac vein → detachment of thrombus → pulmonary thromboembolism → occlusion of pulmonary artery branch → pulmonary infarction. This patient has Antiphospholipid Syndrome (APS) with SLE (positive anti-cardiolipin, anti-dsDNA, ANA, false-positive VDRL) - a hypercoagulable state promoting thrombosis.

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G-34 (Page 34)

1. Term for gross appearance of lung: "Red hepatisation" (if early - lung is red, solid, airless, liver-like) or "Grey hepatisation" (if late - grey, dry). In the context of pulmonary embolism/infarction: "Red (haemorrhagic) infarct" - wedge-shaped haemorrhagic area at the periphery.
2. Cells in alveoli: Haemosiderin-laden macrophages ("heart failure cells" / siderophages) - macrophages containing haemosiderin from phagocytosed RBCs in alveoli. Also fibrin and oedema fluid.
3. Probable diagnosis: Pulmonary embolism with haemorrhagic infarction (given sudden chest pain, collapse in a 70-year-old with likely risk factors).

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G-35 (Page 35)

1. Spleen changes: Congestive splenomegaly (due to portal hypertension from liver cirrhosis). Grossly: enlarged spleen (splenomegaly), firm, dark red/congested. Microscopically: dilated sinusoids, congestion, Gamna-Gandy bodies (foci of old haemorrhage with haemosiderin and calcium deposits), fibrosis.
2. (Question about conditions not fully extracted) Conditions causing congestive splenomegaly:
   • Portal hypertension (cirrhosis, portal vein thrombosis, Budd-Chiari)
   • Right heart failure (chronic passive congestion)
   • Splenic vein thrombosis

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G-36 (Page 36) - G-37

1. Term for liver: "Nutmeg liver" (Chronic passive congestion of liver)
2. Reason for appearance: Chronic venous outflow obstruction (right heart failure → elevated central venous pressure → hepatic vein congestion → centrilobular sinusoidal distension → centrilobular necrosis). The alternating dark-red congested centrilobular areas and pale yellow-tan periportal hepatocytes give a mottled "nutmeg" appearance (like a cut nutmeg).
3. Probable diagnosis: Chronic passive venous congestion of liver due to right heart failure (Cor pulmonale or tricuspid regurgitation)

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G-37 (Page 37) - G-38

1. Clinical sign: Pitting oedema (pressing with a finger leaves an indentation/pit)
2. Causes of oedema (at least three):
   • Hypoproteinaemia (nephrotic syndrome, liver cirrhosis, malnutrition/kwashiorkor)
   • Increased hydrostatic pressure (heart failure, portal hypertension, venous obstruction)
   • Lymphatic obstruction (lymphoedema)
   • Increased vascular permeability (inflammation, anaphylaxis, burns)
   • Sodium and water retention (renal failure, primary hyperaldosteronism)
3. Oedema in renal dysfunction:
   • Nephrotic syndrome: Generalised pitting oedema (facial puffiness/periorbital oedema early, then dependent/ascites) due to hypoalbuminaemia (protein loss in urine → decreased oncotic pressure)
   • Nephritic syndrome/Renal failure: Oedema due to sodium and water retention (decreased GFR → increased renin-angiotensin-aldosterone activation)

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G-38 (Page 38) - G-39

1. Lesion: Splenic infarct - pale/white infarct (since spleen has end-artery supply). Grossly: wedge-shaped area with base on capsule, apex toward hilum; pale, firm, depressed surface.
2. Another organ showing similar findings (pale/white infarct): Kidney (renal infarct) - also wedge-shaped pale infarct due to end-artery supply. Also: heart (myocardial infarct - pale after 18-24 hrs).
3. Major histological finding: Coagulative necrosis - ghost outlines of cells with preserved tissue architecture, loss of nuclei (pyknosis, karyorrhexis, karyolysis), eosinophilic cytoplasm, surrounded by a zone of hyperaemia and inflammatory cells.

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G-39 (Page 39)

1. Diagnosis: Pulmonary Thromboembolism (massive)
2. Etiology: Deep Vein Thrombosis (DVT) of lower limb → detached thrombus → pulmonary artery embolism. Predisposing factors: oral contraceptive pills (OCP) - increase clotting factors, immobility.
3. Virchow's Triad: Three factors predisposing to thrombosis:
   • Endothelial injury (vascular wall damage - atherosclerosis, hypertension, trauma)
   • Abnormal blood flow (stasis or turbulence - immobility, cardiac failure, varicosities)
   • Hypercoagulability (inherited - Factor V Leiden, protein C/S deficiency; acquired - OCP, malignancy, antiphospholipid syndrome, pregnancy)
   Consequences/Fates of thrombus:
   • Propagation (growth of thrombus)
   • Embolisation (detachment and migration)
   • Dissolution (fibrinolysis)
   • Organisation and recanalisation (ingrowth of connective tissue, new channels form)
4. Types of embolism:
   • Thromboembolism (most common)
   • Fat embolism (long bone fractures, liposuction)
   • Air/gas embolism (iatrogenic, decompression sickness/caisson disease)
   • Amniotic fluid embolism (obstetric emergency)
   • Tumour embolism
   • Septic embolism (infective endocarditis)
   • Bone marrow embolism

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G-40 (Page 40)

1. Diagnosis: Non-bacterial thrombotic endocarditis (NBTE) / Marantic endocarditis (associated with malignancy - glioblastoma causing hypercoagulable state)
2. Pathogenesis: Malignancy (glioblastoma) → hypercoagulable state (Trousseau syndrome - mucin-secreting tumours and brain tumours activate coagulation, releasing tissue factor) → sterile thrombi on heart valves (usually mitral/aortic) → vegetations → embolisation → splenic and renal infarcts.
3. Conditions with vegetations and gross differentiation:

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G-41 (Page 41)

1. Diagnosis: Portal hypertension with oesophageal varices due to hepatic cirrhosis (alcoholic liver disease)
2. Splenomegaly: Congestive splenomegaly (due to portal hypertension)
3. The splenectomy specimen likely shows: Enlarged spleen with dilated sinusoids, Gamna-Gandy bodies (siderotic nodules with haemosiderin, fibrous tissue, calcium), and congestion.

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G-42 (Page 42)

1. Diagnosis: Lymphoedema (Filariasis/Elephantiasis) - due to lymphatic obstruction by Wuchereria bancrofti
2. Pathogenesis: Wuchereria bancrofti (mosquito-borne) → adult worms lodge in lymphatics → lymphatic obstruction → lymph accumulates in interstitium → non-pitting oedema → chronic changes: fibrosis, skin thickening, rugosity (elephantiasis). Inguinal lymphadenopathy due to filarial worms causing lymphangitis.
3. Conditions with non-pitting oedema:
   • Lymphoedema (filariasis, post-mastectomy, congenital)
   • Myxoedema (hypothyroidism - accumulation of glycosaminoglycans, especially in pretibial area)
   • Lipoedema
   • Chronic venous insufficiency (late stage - fibrous induration)

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G-43 (Page 43)

1. Probable diagnosis and pathogenesis: Septic shock (secondary to peritonitis from appendicular perforation).
   • Pathogenesis: Perforation → bacteria/endotoxins enter bloodstream → systemic inflammatory response → endotoxin (LPS) activates macrophages → massive release of cytokines (TNF-α, IL-1, IL-6) → vasodilation, increased vascular permeability → distributive shock → multi-organ dysfunction.
2. Types of shock and mechanisms:
   • Cardiogenic: Pump failure (MI, arrhythmia) - decreased cardiac output
   • Hypovolaemic: Reduced blood volume (haemorrhage, burns, dehydration)
   • Distributive/Septic: Vasodilation, maldistribution of blood flow (sepsis, anaphylaxis, neurogenic)
   • Obstructive: Obstruction to flow (PE, tension pneumothorax, cardiac tamponade)
3. Stages of shock:
   • Stage 1 - Compensated (non-progressive): Reflex compensatory mechanisms (sympathetic activation, ADH, RAAS) maintain perfusion
   • Stage 2 - Progressive (decompensated): Compensatory mechanisms fail, hypoperfusion, anaerobic metabolism, lactic acidosis
   • Stage 3 - Irreversible: Cell death, multi-organ failure, death despite resuscitation
4. Organs commonly involved and microscopic findings:
   • Kidney: ATN - tubular necrosis, especially proximal tubules
   • Lung: ARDS - diffuse alveolar damage (hyaline membranes, oedema, neutrophil infiltration)
   • Heart: Subendocardial ischaemic necrosis, fatty change
   • Liver: Centrilobular necrosis, fatty change
   • Brain: Ischaemic encephalopathy, neuronal death
   • Adrenal: Haemorrhagic necrosis (Waterhouse-Friderichsen in meningococcaemia)

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G-44 (Page 44)

1. Diagnosis: Squamous Cell Carcinoma (SCC) of skin (or possibly Malignant Melanoma - foot location)
2. Various sites of presentation (for SCC): Skin (sun-exposed areas, chronic ulcers, scars), oral cavity, lip, larynx, oesophagus, cervix, lung, urinary bladder, penis.
3. Various genetic mutations associated:
   • TP53 mutations (most common in UV-induced SCC)
   • RAS mutations (HRAS, KRAS)
   • CDKN2A/p16 loss (cell cycle dysregulation)
   • Loss of heterozygosity at 3p, 9p
   • For melanoma: BRAF V600E (most common ~50%), NRAS, c-KIT, CDKN2A

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G-45 (Page 45)

1. Three differences between benign and malignant neoplasm:

1. One benign tumour and its malignant counterpart in other organs:
   • Benign: Adenoma (colon) → Malignant: Adenocarcinoma (colon)
   • Benign: Leiomyoma (uterus) → Malignant: Leiomyosarcoma (uterus)
   • Benign: Lipoma (soft tissue) → Malignant: Liposarcoma

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G-46 (Page 46)

1. Diagnosis: Small Cell Carcinoma (SCLC) of lung producing ectopic ACTH (Cushing syndrome due to paraneoplastic ectopic ACTH production). Chest X-ray: hilar/central mass.
2. Substance produced: ACTH (Adrenocorticotrophic hormone) - ectopic production by SCLC causes bilateral adrenal hyperplasia → excess cortisol → Cushing syndrome features (centripetal obesity, moon face, plethora, striae, muscle wasting, osteoporosis, hypertension, easy bruising).
3. Reason for haemoptysis: Tumour invasion/erosion of bronchial blood vessels; central tumour causing mucosal ulceration.
4. Laboratory findings expected:
   • Elevated serum ACTH (very high - ectopic)
   • Elevated 24-hour urinary cortisol
   • Elevated serum cortisol (not suppressible with low-dose dexamethasone, partially with high-dose)
   • Hypokalaemia (ACTH → mineralocorticoid excess)
   • Hyperglycaemia
   • Metabolic alkalosis

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G-47 (Page 47)

1. Diagnosis: Invasive ductal carcinoma of breast (with probable bone metastases - elevated PTHrP and alkaline phosphatase suggest osteolytic bone metastases)
2. Elevated PTHrP: Breast carcinoma cells secrete PTHrP (Parathyroid Hormone-related Peptide) as a paraneoplastic phenomenon → stimulates osteoclasts → osteolytic bone destruction → hypercalcaemia (humoral hypercalcaemia of malignancy). Elevated alkaline phosphatase: Due to osteoblastic activity in response to bone metastases (osteoblastic component), liver metastases (hepatic isoform), or bony destruction with reactive new bone formation.

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G-48 (Page 48)

1. Diagnosis: Metastatic adenocarcinoma in left supraclavicular (Virchow's) lymph node (Troisier's sign). Likely from a gastrointestinal or pancreatic primary (most common causes of Virchow's node metastasis).
2. Thromboembolism: Trousseau syndrome (migratory thrombophlebitis) - mucin-secreting adenocarcinomas (gastric, pancreatic, lung) release mucin and tissue factor → activate coagulation cascade → hypercoagulable state → DVT and pulmonary embolism.
3. Likely primary site: Stomach (most classic for Virchow's node via thoracic duct) or Pancreas, Lung, or other GI tract tumours.

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G-49 (Page 49)

1. Gross and microscopic picture:
   • A: Grossly: soft, encapsulated, yellowish lobulated mass (fat). Microscopically: mature adipocytes with uniform round nuclei pushed to periphery; no atypia; thin fibrous capsule.
   • B: Grossly: large, infiltrative, firm-to-hard mass; areas of necrosis/haemorrhage; ulcerated surface. Microscopically: pleomorphic cells, atypical mitoses, lipoblasts (cells with cytoplasmic fat vacuoles indenting the nucleus) - features of liposarcoma; or pleomorphic undifferentiated sarcoma.
2. Diagnosis:
   • A: Lipoma (benign tumour of adipose tissue)
   • B: Liposarcoma (malignant tumour of adipose tissue) - likely myxoid/round cell or pleomorphic type given rapid growth and ulceration; OR Undifferentiated pleomorphic sarcoma (formerly MFH)

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G-50 (Page 50)

1. Term for rash: Butterfly (malar) rash - erythematous rash over the nose and both cheeks in a butterfly distribution; spares the nasolabial folds.
2. Probable diagnosis: Systemic Lupus Erythematosus (SLE) with Lupus Nephritis
3. Antibodies seen in this condition (at least two):
   • Anti-dsDNA (anti-double stranded DNA) - highly specific for SLE, correlates with disease activity and nephritis
   • Anti-Sm (Anti-Smith) - highly specific for SLE
   • ANA (Antinuclear Antibody) - most sensitive (~95%), not specific
   • Anti-cardiolipin / Antiphospholipid antibodies - associated with thrombosis, miscarriage
   • Anti-histone antibodies - drug-induced lupus
   • Anti-C1q - associated with lupus nephritis

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